Closure device

ABSTRACT

A closure device for closing a bodily passageway is provided. The device includes first and second frames and first and second crossbars. A sheet of biocompatible material is attached to one or more of the frames. The first crossbar extends across the first frame and has terminal crossbar ends connectively linked to separate sites on the first frame; the second crossbar is similarly linked to the second frame. The crossbars are attached to each other at a connection point, and they are each configured to bend away from the connection point when the closure device is deployed to close a bodily passageway. A method of making the closure device is provided, as well as a method for closing a bodily passageway using such a device. Further, a closure device assembly is provided, including a closure device, a delivery catheter housing, and a delivery release member.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a division of U.S. patent application Ser. No.12/813,489, filed Jun. 10, 2010, which is a continuation-in-part of U.S.patent application Ser. No. 12/533,731, published as U.S. publicationno. 2010/0030259, filed on Jul. 31, 2009, which is a continuation of PCTapplication no. PCT/US2008/001422, filed on Feb. 1, 2008, which claimsthe benefit of priority under 35 U.S.C. §119(e) to U.S. ProvisionalApplication No. 60/898,834, filed Feb. 1, 2007, all of which are herebyincorporated by reference in their entireties.

TECHNICAL FIELD

This invention relates generally to medical devices, and particularly,to implantable medical devices for closing bodily passageways, includingthe patent foramen ovale (PFO) and various atrial septal defects (ASDs).

BACKGROUND

A patent foramen ovale is a persistent, one-way, usually flap-likeopening in the wall between the right atrium and left atrium of theheart. In utero, the foramen ovale serves as a physiologic conduit forright-to-left shunting of blood in the fetal heart. Because blood isoxygenated through the umbilical cord, and not through the developinglungs, the circulatory system of the fetal heart allows the blood toflow through the foramen ovale as a physiologic conduit forright-to-left shunting. After birth, with the establishment of pulmonarycirculation, the increased left atrial blood flow and pressure pressesthe septum primum against the walls of the septum secundum, covering theforamen ovale and resulting in functional closure of the foramen ovale.This closure is usually followed by anatomical closure of the foramenovale due to fusion of the septum primum to the septum secundum.

Where anatomical closure of the foramen ovale does not occur, a PFO iscreated. Studies have shown that a relatively large percentage of adultshave a PFO. The presence of a PFO is generally considered to have notherapeutic consequence in otherwise healthy adults. Because left atrial(LA) pressure is normally higher than right atrial (RA) pressure, theflap usually stays closed. Under certain conditions, however, rightatrial pressure can exceed left atrial pressure, creating thepossibility that blood could pass from the right atrium to the leftatrium and blood clots could enter the systemic circulation. It isdesirable that this circumstance be eliminated.

Paradoxical embolism via a PFO is considered in the diagnosis forpatients who have suffered a stroke or transient ischemic attack (TIA)in the presence of a PFO and without another identified cause ofischemic stroke. While there is currently no definitive proof of acause-effect relationship, many studies have confirmed a strongassociation between the presence of a PFO and the risk for paradoxicalembolism or stroke. It has been estimated that in 50% of cryptogenicstrokes, a PFO is present. In addition, there is significant evidencethat patients with a PFO who have had a cerebral vascular event are atincreased risk for future, recurrent cerebrovascular events.

Patients suffering a cryptogenic stroke or a transient ischemic attack(TIA) in the presence of a PFO often are considered for medical therapyto reduce the risk of a recurrent embolic event. Accordingly, patientsat such an increased risk are considered for prophylactic medicaltherapy to reduce the risk of a recurrent embolic event. These patientsare commonly treated with oral anticoagulants to reduce the risk of arecurrent embolic event. However, these anticoagulants have potentiallyadverse side effects, including hemorrhaging, hematoma, and adverseinteractions with other drugs. In addition, use of anticoagulant drugscan alter a person's recovery and necessitate adjustments in a person'sdaily living pattern.

Where anticoagulation is contraindicated, surgery may be employed toclose a PFO. The surgery would typically include suturing a PFO closedby attaching septum secundum to septum primum. Like other open surgicaltreatments, however, this surgery is highly invasive, risky, requiresgeneral anesthesia, and may result in lengthy recuperation.

Nonsurgical closure of PFOs has become possible with the introductionvarious mechanical closure devices, including umbrella devices and thelike, which were initially for percutaneous closure of atrial septaldefects (ASDs; a condition where there is not a septum primum). Thesedevices potentially allow patients to avoid the side effects oftenassociated with anticoagulation therapies and the risks of invasivesurgery.

However, devices for treating heart defects, such as PFO and otheratrial and ventricular septal heart defects have their share ofdrawbacks. The complex anatomical features of PFOs present a challengeto a one size fits all approach. The PFO involves two components, septumprimum and septum secundum. The septum secundum is thicker than septumprimum and exhibits limited mobility and compliance. Failure of thesetwo structures to fuse creates a tunnel-like opening, the PFO. Thedistance of the nonfusion between the two septa determines theparticular size of the PFO, which must be considered in the design of adevice targeting PFOs. Nevertheless, devices are often configured sothat the patient's anatomy must be adjusted to fit the geometry of thedevice. As a consequence, heart tissue may be torn when accommodatingsuch devices.

Conventional nonsurgical closure devices are often technically complex,bulky, have a high septal profile, low radiopacity, and an inability toprovide immediate closure. Additionally, many of the devices have ageometry which tends to prevent the device from remaining flat against,or within the defect once deployed. The varying passageway geometriesoften require multiple sized devices. Moreover, many devices are setapart by a relatively long central section corresponding to the PFOtunnel. By increasing the device profile, the device can presentdifficulties with respect to complete endothelialization. Conventionalclosure devices are often difficult to deploy or reposition, oftenrequire replacement or repositioning, and require relatively largedelivery catheters (for example, 9-10 French or more). In addition, thelarge masses of foreign material associated with the device may lead tounfavorable body adaptation to the device, including thromboses or otherunfavorable reactions. Further drawbacks to nonsurgical closure devicesinclude complications resulting from fractures of the components,conduction system disturbances, perforations of heart tissue, residualleaks, and inability to allow subsequent methods involving transeptalpuncturing.

Accordingly, there is a need for improved low profile closure devicesand simplified delivery methods for immediate closure, which are capableof limiting the amount of foreign material deployed and enhancingclosure stability. The present invention is designed to address a numberof the deficiencies surrounding conventional closure devices.

BRIEF SUMMARY OF THE INVENTION

In one embodiment, the present invention provides a closure device forclosing a bodily passageway. The closure device includes a first frame,a second frame, a first crossbar, and a second crossbar. A sheet ofbiocompatible material is attached to the first frame. The firstcrossbar extends across the first frame. The first crossbar has terminalcrossbar ends connectively linked to separate sites on the first frame.Likewise, the second crossbar extends across the second frame and hasterminal crossbar ends connectively linked to separate sites on thesecond frame. The first and second crossbars are attached to each otherat a connection point, and the first and second crossbars are eachconfigured to bend away from the connection point when the closuredevice is deployed to close a bodily passageway.

In another embodiment, a closure device assembly is provided. Theassembly includes a delivery catheter housing, a delivery releasemember, and a collapsibly disposed closure device, such as the closuredevice described above.

In yet another embodiment, a method for closing a bodily passageway in apatient is provided. The method includes providing a closure deviceassembly, including a delivery catheter housing, a delivery releasemember, and a closure device, such as the closure device describedabove. For example, the closure device includes a first and secondframe, as described above. The method further includes advancing thedelivery catheter housing through the bodily passageway and releasingthe first frame from the delivery catheter housing proximate to a firstopening of the bodily passageway. The method also includes retractingthe delivery catheter housing through the bodily passageway, positioningthe delivery catheter housing proximate to a second opening of thebodily passageway, and disengaging the closure device from the deliveryrelease member to release the second frame of closure device proximateto the second opening of the bodily passageway. The closure device issecured to tissue portions surrounding the bodily passageway, therebyclosing the bodily passageway.

In still another embodiment of the present invention, a method formaking a closure device for closing a bodily passageway is provided. Themethod includes threading one or more first retention members throughone or more first tubular members to create a first frame, and threadingthe first retention member(s) through a first crossbar and a thirdcrossbar. The method further includes fastening the first retentionmember(s) to hold together the first tubular member(s), the firstcrossbar and the third crossbar. Similarly to the foregoing steps, themethod includes threading one or more second retention members thoughone or more second tubular members to create a second frame, threadingthe second retention member(s) through a second crossbar and a fourthcrossbar, and fastening the second retention member(s) to hold togetherthe second tubular member(s), the second crossbar and the fourthcrossbar. The method further includes attaching a central portion of thefirst crossbar to the second crossbar and attaching a central portion ofthe third crossbar to the fourth crossbar. In addition, the methodincludes threading one or more third retention members through adelivery bar and fastening the third retention member(s) to one or moreof the following: the first tubular member(s), the second tubularmember(s), the first retention member(s), or the second retentionmember(s).

Further aspects, features, and advantages of the invention will becomeapparent from consideration of the following description and theappended claims when taken in connection with the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a cross-section view of a heart having a PFO;

FIG. 2 is perspective view of an exemplary closure device according toan embodiment of the present invention;

FIG. 3 is a perspective view of the closure device of FIG. 2, showingthe closure device without biocompatible sheets to provide furtherdetails of the frames, in accordance with the principles of the presentinvention;

FIG. 4 is a right end perspective view of the closure device of FIGS. 2and 3, according to the principles of the present invention;

FIG. 5 is a left end perspective view of the closure device of FIGS.2-4, in accordance with the principles of the present invention;

FIG. 6 is a right end view of the closure device of FIGS. 2-5 deployedin a bodily passageway, having one sheet of biocompatible materialremoved to show details of the frame and crossbar structures, accordingto the principles of the present invention;

FIG. 7 is a left end view of the closure device of FIGS. 2-6 deployed ina bodily passageway, having both sheets of biocompatible materialremoved to show details of the frame and crossbar structures, inaccordance with the principles of the present invention;

FIG. 8 is a side view of the closure device of FIGS. 2-7 deployed in abodily passageway, according to the principles of the present invention;

FIG. 9 is a block diagram illustrating a method for making a closuredevice according to the principles of the present invention;

FIG. 9A is a plan view of a retention member and tubular members forconstructing a frame of a closure device in accordance with theprinciples of the present invention;

FIG. 9B is a plan view of the tubular members and retention member ofFIG. 9A, forming a frame for a closure device according to theprinciples of the present invention;

FIG. 9C is a plan view of the tubular members and retention member ofFIGS. 9A-9B, and a crossbar for constructing a closure device inaccordance with the principles of the present invention;

FIG. 9D is a plan view of the tubular members, retention member, andcrossbar of FIG. 9C, showing the crossbar pulled into place to constructa closure device according to the principles of the present invention;

FIG. 9E is a plan view of the tubular members, retention member andcrossbar of FIGS. 9C-9D, with an additional crossbar for constructing aclosure device in accordance with the principles of the presentinvention;

FIG. 9F is a plan view of the tubular members, retention member, andcrossbars of FIG. 9E, fastened together to construct a frame andcrossbar assembly for a closure device in accordance with the principlesof the present invention;

FIG. 9G is a plan view of the frame and crossbar assembly of FIG. 9F anda second set of tubular members, retention member, and additionalcrossbar to construct another frame and crossbar assembly to construct aclosure device, according to the principles of the present invention;

FIG. 9H is a plan view of the frame and crossbar assembly, second set oftubular members, retention member, and additional crossbar of FIG. 9G,with the additional crossbar threaded through a coupling member of theframe and crossbar assembly to construct a closure device, in accordancewith the principles of the present invention;

FIG. 9I is a plan view of the frame and crossbar assembly, second set oftubular members, retention member, and additional crossbar of FIGS.9G-9H, including another additional crossbar for constructing a closuredevice, according to the principles of the present invention;

FIG. 9J is a plan view of the frame and crossbar assembly, tubularmembers, retention member, and crossbars of FIG. 9I, with the additionalcrossbar threaded through a coupling member to construct a closuredevice, in accordance with the principles of the present invention;

FIG. 9K is a plan view of a frame and crossbar assembly including theelements of FIGS. 9I-9J for constructing a closure device, according tothe principles of the present invention;

FIG. 9L illustrates a method for forming a delivery bar for constructinga closure device, in accordance with the principles of the presentinvention;

FIG. 9M is a plan view of the frame and crossbar assembly of FIG. 9K,including the delivery bar of FIG. 9L, for constructing a closure deviceaccording to the principles of the present invention;

FIG. 9N is a plan view of the frame, crossbar, and deliver bar assemblyof FIG. 9M, with the delivery bar secured to a frame to construct aclosure device, in accordance with the principles of the presentinvention;

FIG. 10A is a cross-sectional view of the distal end of a closure deviceassembly inserted through a bodily passageway, according to theprinciples of the present invention;

FIG. 10B is a side view of the distal end of the closure device assemblyand bodily passageway of FIG. 10A, showing a closure device partiallyreleased from the distal end of the closure device assembly, inaccordance with the principles of the present invention;

FIG. 10C is a side view of the distal end of the closure device assemblyand bodily passageway of FIGS. 10A-10C, showing retraction of a lockingcatheter sheath and disengagement of the closure device from thedelivery release member, in accordance with the principles of thepresent invention;

FIG. 11 is a cross-sectional view of the distal end of another closuredevice assembly, according to the principles of the present invention;and

FIG. 12 is a block diagram illustrating a method for closing a bodilypassageway in a patient, according to the principles of the presentinvention.

DETAILED DESCRIPTION OF THE INVENTION

A closure device for closing or occluding bodily passageways, includingseptal openings of the heart is provided. As used herein, the terms“opening”, “bodily opening”, “passageway”, and “bodily passageway” areinterchangeably used to refer to a bodily opening, aperture, canal,conduit, or duct, including but not limited to septal openings, heartvalves, blood vessels, vessel punctures, bile ducts, and the like.Unlike certain other PFO closure devices in the prior art, the closuredevice of the present invention can provide reduced foreign materials, alow profile, self-centering capacity, good radiopacity, simplifieddelivery, and an increased capacity for immediate closure of a varietyof passageway sizes. Without wishing to be bound by a particular theoryor to in any way limit the scope of the appended claims and theirequivalents, it is believed that incorporation of bioremodelablematerial capable of causing angiogenesis and replacement by host tissuesaccording to the present invention provides a more stable and permanentclosure compared to conventional closure devices.

FIG. 1 is a schematic front view of a heart 2 with a septal defect, suchas patent foramen ovale (PFO). The heart 1 has a right atrium 2, rightventricle 3, left atrium 4, and a left ventricle 5. The septum 6 betweenthe right atrium 2 and the left atrium 4 comprises a septum primum 7 anda septum secundum 8. The PFO 9 is an opening in the septum 6 that hasnot properly closed. Where a PFO 9 is present, the septum primum 7typically overlaps the septum secundum 8 and the higher pressure in theleft atrium 4 typically closes the flaps of the septum primum 7 and theseptum secundum 8 so that blood does not leak between the atria 2 and 4.However, when there is a pressure change in the chest, the flaps mayseparate permitting blood to flow through the PFO and between the atria2 and 4.

Now referring to FIG. 2, closure device for closing a bodily passage isprovided and generally indicated at reference numeral 20. The closuredevice 20 includes a first frame 22 and a second frame 24. The first andsecond frames 22, 24 may be generally circular, as shown, or elliptical,or having any other suitable shape, within the spirit and scope of thepresent invention. For example, the frames could have a polygonal shape.The frames 22, 24 may have straight or curved edges.

The frames 22, 24 may be in the form of a closed or substantially closedwire, coil, tubular structure, or bar-like structure. One or both of theframes 22, 24 may be discontinuous, provided that at least one of theframes 22, 24 is capable of supporting a sheet of biocompatible materialonto a frame configuration suitable for covering a septal opening, suchas a PFO. Exemplary polygonal shapes include, but are not limited totriangle, quadrilateral, square, pentagon, hexagon, octagon, and thelike. Circular shapes include circle, oval, ellipse, and the like, byway of example.

Generally, the frames 22, 24 have a first configuration wherein thesides and bends generally lie within a single, flat plane, and a secondconfiguration whereby sides and bends are brought in closer proximity toone another when the frames 22, 24 are collapsibly disposed in adelivery catheter. Further, the frames 22, 24 of FIGS. 2 and 3 are shownpulled apart with cords 25, to better show the detail of the frames 22,24. In the pulled-apart configuration, the frames 22, 24 may be bent andmay not lie in a completely flat plane.

In one aspect, the frames 22, 24 are formed from one or more tubularmembers. The tubular members could be, for example, in the form ofcoils, bars, wires, or other hollow tubular members. The frames 22, 24may be formed from a variety of wire or non-wire materials differing inshape and material substance. For example, the frames 22, 24 may beformed from flat or rounded wires having a variety of cross-sectionalshapes (for example, oval, delta, D-, and the like). The frames 22, 24may each be formed from a single tubular member or other material havinga plurality of sides and bends each interconnecting adjacent sides, orthey may each be formed from multiple tubular members. A closedcircumferential frame 22, 24 may be formed a single piece of continuous,circumferential tube or coil, for example, or it may be joined by anysuitable attachment mechanism, including, but not limited to cannula andsolder, spot welding, and the like.

Additionally, the frames 22, 24 may be formed from one or more linkedcoils or laser cut from a tube or bar. Generally, the frames 22, 24 maybe formed from metallic material, such as platinum, stainless steel orNitinol. The tube or bar may be hollow or filled. Additional methods forforming or manipulating a circumferential frame are described indescribed in U.S. Patent Application Publication No. 2001/0039450 A1,the disclosures of which are expressly incorporated by reference herein.

When using frames 22, 24 that are formed from coils or hollow tubularmembers, wires, threaded materials, sutures, adhesives or metalliccouplers may be used to join the coil or hollow tubular member ends.Alternatively, the ends may be directly joined to one another bysoldering or welding. Alternatively, the frames 22, 24 may beprefabricated as a continuous closed structure, or as a non-continuousstructure. The use of a coil in a frame 22, 24 can provide additionalflexibility for repositioning or removal of the closure device 20 whenusing snares or other suitable removal or retrieval devices known tothose of skill in the art.

The frame 22, 24 may be variably sized depending on the size of thebodily passageway or septal opening, such as a PFO. In particular, theframes 22, 24 are each configured to completely overlap the opening atone end of the bodily passageway. Accordingly, the frames 22, 24 may beconfigured with a diameter size or (diagonal size for polygonal frames)between about 5 mm and about 50 mm, preferably between about 10 mm andabout 30 mm, or between about 15 mm and about 25 mm. By way of example,a frame 22, 24 having a diameter size (or diagonal size for polygonalframes) between about 18 and about 20 mm may be used for closing mostPFOs, while a size between about 25 and about 30 mm may be used forclosing PFOs and other septal defects. Accordingly, the frames 22, 24may be configured with a diameter size ranging from about 15 to about 35mm, preferably between about 18 to about 30 mm.

The first and second frames 22, 24 are each covered by a sheet ofbiocompatible material. For example a first sheet 26 of biocompatiblematerial is attached to the first frame 22, and a second sheet 28 ofbiocompatible material is attached to the second frame 24. The frames22, 24 may be partially or substantially covered by the sheets 26, 28 ofbiocompatible material. In some embodiments, however, one of the frames22, 24 may not have a biocompatible material sheet covering it.

As used herein, the term “biocompatible” refers to a material that issubstantially non-toxic in the in vivo environment of its intended use,and that is not substantially rejected by the patient's physiologicalsystem or is non-antigenic. This can be gauged by the ability of amaterial to pass the biocompatibility tests set forth in InternationalStandards Organization (ISO) Standard No. 10993; the U.S. Pharmacopeia(USP) 23; or the U.S. Food and Drug Administration (FDA) blue bookmemorandum No. G95-1, entitled “Use of International Standard ISO-10993,Biological Evaluation of Medical Devices Part-1: Evaluation andTesting.” Typically, these tests measure a material's toxicity,infectivity, pyrogenicity, irritation potential, reactivity, hemolyticactivity, carcinogenicity, immunogenicity, and combinations thereof. Abiocompatible structure or material, when introduced into a majority ofpatients, will not cause a significantly adverse, long-lived orescalating biological reaction or response, and is distinguished from amild, transient inflammation which typically accompanies surgery orimplantation of foreign objects into a living organism.

Bioremodelable materials, including collagenous ECM materials andintestinal submucosal tissue materials, provide a preferred source ofbiocompatible sheet 26, 28 materials for attachment to the frames 22,24. The bioremodelable material used for the sheets 26, 28 may beconfigured to close a bodily passageway.

As used herein, the term “bioremodelable” refers to a natural orsynthetic material that is bioresorbable and capable of inducingangiogenesis, tissue remodeling, or both in a subject or host.“Angiogenesis” and “angiogenic” refer to bioactive properties, which maybe conferred by a bioremodelable material through the presence of growthfactors and the like, which are defined by formation of capillaries ormicrovessels from existing vasculature in a process necessary for tissuegrowth, where the microvessels provide transport of oxygen and nutrientsto the developing tissues and remove waste products. “Bioresorbable”refers to those materials of either synthetic or natural origin which,when placed in a living body, are degraded through either enzymatic,hydrolytic or other chemical reactions or cellular processes intoby-products which are either integrated into, or expelled from, thebody. It is recognized that in the literature, the terms “resorbable”,“absorbable”, and “bioabsorbable” are frequently used interchangeably.

A bioremodelable material includes at least one bioactive agent capableof inducing angiogenesis or tissue remodeling. One or more bioactiveagents in the bioremodelable material may stimulate infiltration ofnative cells into an acellular matrix, and formation of new bloodvessels (capillaries) growing into the matrix to nourish theinfiltrating cells (angiogenesis). Additionally, the bioactive agentsmay cause the degradation or replacement of the bioremodelable materialby endogenous tissue. The bioremodelable material may include anaturally derived collagenous ECM tissue structure present in, forexample, native submucosal tissue sources, including, but not limited tosmall intestine submucosal (SIS) tissue, or it may include any one of avariety of different non-submucosal ECM-containing tissue materials orsynthetic, bioresorbable non-ECM materials capable of inducingangiogenesis and tissue remodeling in a host.

The term “submucosa” refers to a natural collagen-containing tissuestructure removed from a variety of sources including the alimentary,respiratory, intestinal, urinary or genital tracts of warm-bloodedvertebrates. Submucosal material according to the present inventionincludes tunica submucosa, but may include additionally adjacent layers,such the lamina muscularis mucosa and the stratum compactum. Asubmucosal material may be a decellularized or acellular tissue, whichmeans it is devoid of intact viable cells, although some cell componentsmay remain in the tissue following purification from a natural source.Alternative embodiments (for example, fluidized compositions and thelike) include submucosal material expressly derived from a purifiedsubmucosal matrix structure. Submucosal materials according to thepresent disclosure are distinguished from collagen materials in otherclosure devices that do not retain their native submucosal structures orthat were not prepared from purified submucosal starting materials firstremoved from a natural submucosal tissue source.

The term “small intestinal submucosa” (SIS) refers to a particularsubmucosal tissue structure removed from a small intestine source, suchas pig.

The “sheet of biocompatible material” and “sheet of bioremodelablematerial” refer to one or more biocompatible or bioremodelable tissuelayers or synthetic polymeric layers formed into a sheet or compositethereof. A sheet of biocompatible or bioremodelable material mayinclude, for example, one or more naturally-derived tissue layerscontaining an ECM scaffold, one or more biocompatible polymeric layers,or combinations thereof. The sheet of biocompatible or bioremodelablematerial can be in the form of a single tissue or polymeric layer or aplurality of tissue or polymeric layers in form of laminates,composites, or combinations thereof. Preferred bioremodelable materialsinclude naturally derived tissues with ECMs possessing biotropicproperties, including in certain forms angiogenic collagenous ECMs.Preferred ECMs includes naturally-derived collagenous tissue materialretaining native matrix configurations and bioactive agents, such asgrowth factors, which serve to facilitate tissue remodeling. In thealternative, collagen-based materials formed by separately purifyingnatural collagen and other associated components away from their nativethree dimensional matrix configurations or bioactive agents, includinggrowth factors, may be used. Suitable collagenous ECMs include thosederived from a variety of native tissues, including but not limited to,intestine, stomach, bladder, liver, fascia, skin, artery, vein,pericardium, pleura, heart valve, dura mater, ligament, tendon, bone,cartilage, bladder, liver, including submucosal tissues therefrom, renalcapsule membrane, dermal collagen, serosa, mesenterium, peritoneum,mesothelium, various tissue membranes and basement membrane layers,including liver basement membrane, and the like. Suitable submucosatissue materials for these purposes include, for instance, intestinalsubmucosa, including small intestinal submucosa, stomach submucosa,urinary bladder submucosa, and uterine submucosa. A particularlypreferred ECM material is porcine SIS material. Commercially availableECM materials capable of remodeling to the qualities of its host whenimplanted in human soft tissues include porcine SIS material(Surgisi^(SM) and Oasi^(SM) lines of SIS materials, Cook Biotech Inc.,West Lafayette, Ind.) and bovine pericardium (Peri-Strip^(SM), SynovisSurgical Innovations, St. Paul, Minn.).

As prepared, the submucosa material and any other ECM used mayoptionally retain growth factors or other bioactive components native tothe source tissue. For example, the submucosa or other ECM may includeone or more growth factors such as basic fibroblast growth factor(FGF-2), transforming growth factor beta (TGF-beta), epidermal growthfactor (EGF), platelet derived growth factor (PDGF), and other growthfactors known to those of skill in the art. As well, submucosa or otherECM used in the invention may include other biological materials such asheparin, heparin sulfate, hyaluronic acid, fibronectin and the like.Thus, generally speaking, the submucosa or other ECM material mayinclude a bioactive component that induces, directly or indirectly, acellular response such as a change in cell morphology, proliferation,growth, protein expression, gene expression, or combinations thereof.

Submucosa or other ECM materials of the present invention can be derivedfrom any suitable organ or other tissue source, usually sourcescontaining connective tissues. The ECM materials processed for use inthe invention will typically include abundant collagen, most commonlybeing constituted at least about 80% by weight collagen on a dry weightbasis. Such naturally-derived ECM materials will for the most partinclude collagen fibers that are non-randomly oriented, for instanceoccurring as generally uniaxial or multi-axial but regularly orientedfibers. When processed to retain native bioactive factors, the ECMmaterial can retain these factors interspersed as solids between, uponor within the collagen fibers. Particularly desirable naturally-derivedECM materials for use in the invention will include significant amountsof such interspersed, non-collagenous solids that are readilyascertainable under light microscopic examination with specificstaining. Such non-collagenous solids can constitute a significantpercentage of the dry weight of the ECM material in certain inventiveembodiments, for example, at least about 1%, at least about 3%, and atleast about 5% by weight in various embodiments of the invention.

The submucosa or other ECM material used in the present invention mayalso exhibit an angiogenic character and thus be effective to induceangiogenesis in a host engrafted with the material. In this regard,angiogenesis is the process through which the body makes new bloodvessels to generate increased blood supply to tissues. Thus, angiogenicmaterials, when contacted with host tissues, promote or encourage theinfiltration of new blood vessels. Methods for measuring in vivoangiogenesis in response to biomaterial implantation have recently beendeveloped. For example, one such method uses a subcutaneous implantmodel to determine the angiogenic character of a material (C. Heeschenet al., Nature Medicine 7 (2001), No. 7, 833-839). When combined with afluorescence microangiography technique, this model can provide bothquantitative and qualitative measures of angiogenesis into biomaterials(C. Johnson et al., Circulation Research 94 (2004), No. 2, 262-268).

In addition to, or as an alternative to the inclusion of nativebioactive components, non-native bioactive components such as thosesynthetically produced by recombinant technology or other methods, maybe incorporated into the submucosa or other ECM tissue. These non-nativebioactive components may be naturally-derived or recombinantly producedproteins that correspond to those natively occurring in the ECM tissue,but perhaps of a different species (for example, human proteins appliedto collagenous ECMs from other animals, such as pigs). The non-nativebioactive components may also be drug substances. Illustrative drugsubstances that may be incorporated into or onto the ECM materials usedin the invention include, for example, antibiotics or thrombus-promotingsubstances such as blood clotting factors, for example, thrombin,fibrinogen, and the like. These substances may be applied to the ECMmaterial as a premanufactured step, immediately prior to the procedure(for example, by soaking the material in a solution containing asuitable antibiotic such as cefazolin), or during or after engraftmentof the material in the patient.

Submucosa or other ECM tissue used in the invention is preferably highlypurified, for example, as described in U.S. Pat. No. 6,206,931 to Cooket al., which is incorporated by reference herein. Thus, preferred ECMmaterial will exhibit an endotoxin level of less than about 12 endotoxinunits (EU) per gram, more preferably less than about 5 EU per gram, andmost preferably less than about 1 EU per gram. As additionalpreferences, the submucosa or other ECM material may have a bioburden ofless than about 1 colony forming units (CFU) per gram, more preferablyless than about 0.5 CFU per gram. Fungus levels are desirably similarlylow, for example, less than about 1 CFU per gram, more preferably lessthan about 0.5 CFU per gram. Nucleic acid levels are preferably lessthan about 5 μg/mg, more preferably less than about 2 μg/mg, and viruslevels are preferably less than about 50 plaque forming units (PFU) pergram, more preferably less than about 5 PFU per gram. These andadditional properties of submucosa or other ECM tissue taught in U.S.Pat. No. 6,206,931 may be characteristic of the submucosa tissue used inthe present invention.

A preferred purification process involves disinfecting the submucosaltissue source, followed by removal of a purified matrix including thesubmucosa. It is thought that delaminating the disinfected submucosaltissue from the tunica muscularis and the tunica mucosa minimizesexposure of the submucosa to bacteria and other contaminants and betterpreserves the aseptic state and inherent biochemical form of thesubmucosa, thereby potentiating its beneficial effects. Alternatively,the ECM- or submucosa may be purified a process in which thesterilization step is carried out after delamination as described inU.S. Pat. Nos. 5,993,844 and 6,572,650.

The stripping of the submucosal tissue source is preferably carried outby utilizing a disinfected or sterile casing machine, to producesubmucosa, which is substantially sterile and which has been minimallyprocessed. A suitable casing machine is the Model 3-U-400 StridhsUniversal Machine for Hog Casing, commercially available from the ABStridhs Maskiner, Gotoborg, Sweden. As a result of this process, themeasured bioburden levels may be minimal or substantially zero. Othermeans for delaminating the submucosa source can be employed, including,for example, delaminating by hand.

Following delamination, submucosa may be sterilized using anyconventional sterilization technique including propylene oxide orethylene oxide treatment and gas plasma sterilization. Sterilizationtechniques which do not adversely affect the mechanical strength,structure, and biotropic properties of the purified submucosa arepreferred. Preferred sterilization techniques also include exposing thegraft to ethylene oxide treatment or gas plasma sterilization.Typically, the purified submucosa is subjected to two or moresterilization processes. After the purified submucosa is sterilized, forexample, by chemical treatment, the matrix structure may be wrapped in aplastic or foil wrap and sterilized again using electron beam or gammairradiation sterilization techniques.

Bioremodelable materials, including ECMs according to the presentinvention, may be isolated and used in the form of intact naturalsheets, tissue layers, or strips, which may be optimally configured froma native, wet, fluidized, or dry formulation or states, into sheets,knitted meshes, or porous scaffolds, using one or more of the following,including stretching, chemical crosslinking, lamination underdehydrating conditions, compression under dehydrating conditions, inaccordance with teachings set forth in U.S. Pat. Nos. 6,206,931 and6,358,284; U.S. Patent Application Publication Nos. 2006/0201996,2006/0052816, 2005/0249772, and 2004/0166169, the disclosures of whichare expressly incorporated by reference herein.

In addition, bioremodelable materials according to the present inventionmay be treated by controlled autolysis to render the materialssubstantially acellular and less susceptible to post-implantationmineralization as described in U.S. Pat. No. 5,595,571, 5,720,777,5,843,180, 5,843,181, and U.S. Patent Application Publication Nos.2005/020612, the disclosures of which are expressly incorporated byreference herein.

The bioremodelable material as used herein may be designed to promoteangiogenesis and endothelialization of the implanted closure device 20.In particular, the bioremodelable material may be provided to be capableof remodeling the surrounding tissues, such that upon implantation, in apatient, the sheet of bioremodelable material is degraded and replacedby the patient's endogenous tissues. As the sheet of bioremodelablematerial is remodeled by host tissues, the bodily opening becomes stablyclosed, obviating concerns about migration of the device.

Bioremodelable sheet materials provide a preferred source ofbiocompatible sheet materials for attachment to the frame. However,other biocompatible sheet materials may be used in place ofbioremodelable sheet material, including composites thereof.Biocompatible sheet materials include a variety of natural or syntheticpolymeric material known to those of skill in the art which can beformed into a flexible sheet material covering the above describedframes 22, 24. Exemplary biocompatible sheet materials include polymericmaterials; fibrous materials; thrombogenic fibrous materials, and othermaterials known to those of skill in the art.

Biocompatible sheet materials may be formed from fibers, or any suitablematerial (natural, synthetic, or combination thereof) that is pliable,strong, resilient, elastic, and flexible. The material should bebiocompatible or capable of being rendered biocompatible by coating,chemical treatment, or the like. Thus, in general, the material maycomprise a synthetic biocompatible material that may include, forexample, bioresorbable materials such as polylactic acid (PLA),polyglycolic acid (PGA), polycaprolactone (PCL), polydioxanone (PDO),trimethylene carbonate (TMC), polyvinyl alcohol (PVA), and copolymers orblends thereof; polyurethanes, including THORALON™ (THORATEC,Pleasanton, Calif.), as described in U.S. Pat. Nos. 4,675,361,6,939,377, and U.S. Patent Application Publication No. 2006/0052816, thedisclosures of which are incorporated by reference herein; celluloseacetate, cellulose nitrate, silicone, polyethylene teraphthalate,polyamide, polyester, polyorthoester, polyanhydride, polyether sulfone,polycarbonate, polypropylene, high molecular weight polyethylene,polytetrafluoroethylene, or mixtures or copolymers thereof, apolyanhydride, polycaprolactone, polyhydroxy-butyrate valerate,polyhydroxyalkanoate, or another polymer able to be made biocompatible.

Thrombogenic fibrous materials include synthetic or natural fibrousmaterial having thrombogenic properties. Exemplary thrombogenic fibrousmaterials include, but are not limited to, DACRON, cotton, silk, wool,polyester thread and the like.

The polymeric materials may include a textile material. The textileincludes fibers and may take many forms, including woven (includingknitted) and non-woven. Preferably, the fibers of the textile comprise asynthetic polymer. Preferred textiles include those formed frompolyethylene terephthalate, polytetrafluoroethylene (PTFE), and expandedpolytetrafluoroethylene (ePTFE). These materials are inexpensive, easyto handle, have good physical characteristics and are suitable forclinical application. These materials may be attached to or rolledaround a hollow tube or coil as described above.

Examples of biocompatible materials from which textiles can be formedinclude polyesters, such as poly(ethylene terephthalate); fluorinatedpolymers, such as polytetrafluoroethylene (PTFE) and fibers of expandedPTFE; and polyurethanes. In addition, materials that are not inherentlybiocompatible may be subjected to surface modifications in order torender the materials biocompatible. Examples of surface modificationsinclude graft polymerization of biocompatible polymers from the materialsurface, coating of the surface with a crosslinked biocompatiblepolymer, chemical modification with biocompatible functional groups, andimmobilization of a compatibilizing agent such as heparin or othersubstances. Thus, any fibrous material may be used to form a textilematerial, provided the final textile is biocompatible. Polymericmaterials that can be formed into fibers suitable for making textilesinclude polyethylene, polypropylene, polyaramids, polyacrylonitrile,nylons and cellulose, in addition to polyesters, fluorinated polymers,and polyurethanes as listed above. Preferably the textile is made of oneor more polymers that do not require treatment or modification to bebiocompatible. More preferably, the textile is made of a biocompatiblepolyester. Examples of biocompatible polyesters include DACRON (DUPONT,Wilmington, Del.) and TWILLWEAVE MICREL (VASCUTEK, Renfrewshire,Scotland).

Textile materials may be woven (including knitted) textiles or nonwoventextiles. Nonwoven textiles are fibrous webs that are held togetherthrough bonding of the individual fibers or filaments. The bonding canbe accomplished through thermal or chemical treatments or throughmechanically entangling the fibers or filaments. Because nonwovens arenot subjected to weaving or knitting, the fibers can be used in a crudeform without being converted into a yarn structure. Woven textiles arefibrous webs that have been formed by knitting or weaving. The woventextile structure may be any kind of weave including, for example, aplain weave, a herringbone weave, a satin weave, or a basket weave.

Woven fabrics may have any desirable shape, size, form andconfiguration. For example, the fibers of a woven fabric may be filledor unfilled. Examples of how the basic unfilled fibers may bemanufactured and purchased are indicated in U.S. Pat. No. 3,772,137, byTolliver, disclosure of which is incorporated by reference. Fiberssimilar to those described are currently being manufactured by theDuPont Company from polyethylene terephthalate (often known as “DACRON”when manufactured by DuPont), and by other companies from varioussubstances.

Non-native bioactive components, such as those synthetically produced byrecombinant technology or other methods, may be incorporated into theseother biocompatible materials. These non-native bioactive components maybe naturally-derived or recombinantly produced proteins, such as growthfactors, which are normally found in ECM tissues. These proteins may beobtained from or engineered from any animal species. The non-nativebioactive components may also be drug substances. Illustrative drugsubstances that may be incorporated into or onto the ECM materials usedin the invention include, for example, antibiotics or thrombus-promotingsubstances such as blood clotting factors, for example, thrombin,fibrinogen, and the like. These substances may be applied to thebiocompatible material as a premanufactured step, immediately prior tothe procedure (for example, by soaking the material in a solutioncontaining a suitable antibiotic such as cefazolin), or during or afterengraftment of the material in the patient.

ECM sheet materials or bioremodelable sheet materials formed from one ormore layers of intestinal submucosal tissue are particularly preferredsources of bioremodelable materials for covering the frames 22, 24.However, other biocompatible sheet 26, 28 materials may be used in placeof bioremodelable sheet material, including composites thereof.Exemplary biocompatible sheet materials include natural or syntheticpolymeric or fibrous sheet materials, including DACRON,polytetrafluoroethylene (PTFE), expanded polytetrafluoroethylene(ePTFE), cotton, silk, wool, polyester, combinations thereof, and thelike, which are further described below.

The sheets 26, 28 of material may include a flexible, pliable materialconfigured onto the frames 22, 24 to project into a passageway,substantially conforming to one or more portions defining thepassageway. The sheets 26, 28 may be sized or pre-stretched inaccordance with a variety of desired three dimensional conformations,shapes, depths, and sizes suitable for closing or occluding a bodilypassageway. The sheets 26, 28 may be laid flat over the frames 22, 24,or they may have a contoured shape, such as a dome shape. For example,the sheets 26, 28 of material may be applied to each of the frames 22,24 whereby the cross-sectional area of the sheets 26, 28 are greaterthan the cross-sectional areas of the frames 22, 24. Thus, the sheets26, 28 of material may be configured to take on a three dimensionalconformation when deployed. Depending on the configuration of itsattachment to elements of the closure device 20, the sheets 26, 28 ofbiocompatible material can adapt to a variety of bodily passagewayshapes and sizes.

The sheets 26, 28 of biocompatible or bioremodelable material may beattached to the frames 22, 24 by any suitable attachment method. Forexample, the sheets 26, 28 of biocompatible of bioremodelable materialmay be attached by sutures 29. Alternative attachment methods include,but are not limited to, use of biological adhesives, use of chemicalcross-linking agents, crimping, tissue welding, heat welding, pressurewelding, heat source, light source, radiofrequency, lasering, otherenergy sources, and the like. Methods for attaching sheet materials toframes are described in U.S. Patent Application Publication No.2001/0039450 A1, the disclosures of which are expressly incorporated byreference herein.

In the embodiment of FIG. 2, the sheets 26, 28 of biocompatible materialare folded over the frames 22, 24 to substantially cover the frames 22,24, and sutures 29 are used to sew the biocompatible sheets 26, 28around the periphery of the frames 22, 24.

FIG. 3 illustrates the closure device 20 of FIG. 2 without the sheets26, 28 of biocompatible material and without the cords 25, in order toshow the frames 22, 24 in more detail. Each frame 22, 24 comprises twocoils 30. Together, the coils 30 form a closed ring, each frame coil 30defining a hemispheric coil ring portion. The coils 30 are hollow tubeshaving retention members 32, 35 such as wires, disposed therein, whichwill be described in further detail below. The retention members 32, 35extend through the lumens of the coils 30 of the first and second frames22, 24 and connect crossbars 34, 36, 38, 40 to the frames 22, 24. Inthis embodiment, a first retention member 32 extends through the lumensof the coils 30 of the first frame 22 and the lumens of the coils 43 ofthe first crossbar 34 and the third crossbar 38; and a second retentionmember 35 extends through the lumens of the coils 30 of the second frame24 and the lumens of the coils 43 of the second crossbar 36 and thefourth crossbar 40.

For example, a first crossbar 34 extends across the first frame 22 andhas terminal ends 42 connectively linked to separate sites on the firstframe 22. “Connectively linked” and “connectively linking”interchangeably refer to the joining, adhering, bonding, attaching, orthe like. In other words, the terminal ends 42 are connected todiscontinuous sites on the circumference of the first frame 22. In thisembodiment, the terminal ends 42 of the first crossbar 34 areconnectively linked to opposite sides of the first frame 22. Likewise, asecond crossbar 36 extends across the second frame 24 and has terminalends 42 connectively linked to separate sites on the second frame 24,similarly to the configuration of the first crossbar 34 and the firstframe 22.

The first and second crossbars 34, 36 are attached to each other via acoupling member 44. In one embodiment, the coupling member 44 is formedfrom a small hollow cannula or band co-encircling the first and secondcrossbars 34, 36, which may be a marker band having radiopaqueproperties, although the radiopaque properties are optional for thepresent invention. The coupling member 44 may be formed from anymaterial suitable for coupling or joining the crossbars 34, 36. Thecoupling member 44 is preferably formed from a metallic materialsuitable for joining device components of the present invention,including but not limited to platinum, stainless steel, or Nitinol.

In this embodiment, the coupling member 44 is a marker band, but thecoupling member 44 could alternatively or additionally include a suture,or a wire, for example, or any other suitable coupling device. Further,the first and second crossbars 34, 36 could also or alternatively bejoined together, by welding, soldering, or an adhesive, by way ofexample.

In the present embodiment, a third crossbar 38 also extends across thefirst frame 22 and has terminal ends 42 connectively linked to separatesites on the first frame 22. For example, each terminal end 42 of thethird crossbar 38 is located on an opposite side of the first frame 22.A fourth crossbar 40 extends across the second frame 24, similarly tothe configuration of the rest of the crossbars 34, 36, 38, and hasterminal ends 42 connectively linked to separate sites on the secondframe 24. The third and fourth crossbars 38, 40 are attached to eachother via a coupling member 46, which may be similar to the couplingmember 44 attaching the first and second crossbars 34, 36. Like thefirst and second crossbars 34, 36, the third and fourth crossbars 38, 40may be attached additionally or alternatively in any suitable manner,such as the ways described above for the first and second crossbars 34,36.

In FIGS. 2 and 3, sutures 48 surround the coupling members 44, 46, whichaid in coupling the crossbars 34, 36, 38, 40, and aid in keeping thecoupling members 44, 46 fairly centralized on the crossbars 34, 36, 38,40. Therefore, a central portion of the first crossbar 34 is attached toa central portion of the second crossbar 36; and a central portion ofthe third crossbar 38 is attached to a central portion of the fourthcrossbar 40. In this embodiment, the “central portion” of a crossbarrefers to a position not more than 30% away from a geometric center ofthe crossbar.

The first and second crossbars 34, 36 are attached to each other at afirst connection point 50. The first and second crossbars 34, 36 areeach configured to bend away from the first connection point 50 when theclosure device 20 is deployed in a bodily passageway. Likewise, thethird and fourth crossbars 38, 40 are attached to each other at a secondconnection point 52. The third and fourth crossbars 38, 40 are eachconfigured to bend away from the second connection point 52 when theclosure device 20 is deployed in a bodily passageway.

FIGS. 2 and 3 exemplify closure devices 20 having a plurality ofconnected coils (or tubular members) 30 connected by one or moreretention members or wires 32, 35. Any one of the first and secondframes 22, 24, frame coils 30, crossbars 34, 36, 38, 40, crossbar coils43, or hollow tubular members thereof may be independently linked to oneor more wires or retention members, or they may be interlinked to otherdevice components by one or more wires or loop structures in one or moreadditional steps.

Accordingly, as shown in the embodiment depicted in FIGS. 2 and 3, aclosure device 20 may include two crossbar coils 43 connected to twoframe coils 30 by wires 32 or 35. Use of any of the above describedattachment means may be employed to directly or indirectly connect aframe 22, 24 to the crossbars 34, 36, 38, 40.

To facilitate the joining of one or more crossbar coils 43 to any one ofthe frame coils 30, or to facilitate the joining of the frames 22, 24 tothe sheets 26, 28 of biocompatible or bioremodelable material, any oneof the various coiled structures may be partially stretched to createinterrupted regions or open grooves to facilitate linkage between coilsand/or biocompatible materials using for example, wires 32, 35 orsutures 29. For example, open area crossbar coil 43 grooves mayfacilitate linkages between the first and second crossbars 34, 36 orbetween the third and fourth crossbars 38, 40 by providing open areaconnections to facilitate wire exchanges between the crossbar coil 43grooves. Open area coil grooves may also provide open area connectionsfacilitating suture exchanges between a frame coil 30 and a sheet 26, 28of biocompatible material.

In addition to being attached to one or more of the frames 22, 24, thesheets 26, 28 of biocompatible material may be additionally attachedalong a portion of one or more of the crossbars 34, 36, 38, 40 or alongthe length of one or more of the crossbars in their entireties.Alternatively, the sheets 26, 28 of biocompatible material may beattached to one or both of the first and second frames 22, 24 only.

In some embodiments, a single wire 32 may be used to link the firstframe 22, the first crossbar 34, and the third crossbar 38. Moreparticularly, a single wire 32 may be threaded through the lumens of thelinear frame coils 30 of the first frame 22 to circularize the firstframe 22. The single wire 32 may be further threaded through the linearcrossbar coil 43 of the first crossbar 34 and the linear crossbar coil43 of the third crossbar 38, to connectively link the circularized framecoil 30 of the first frame 22 to the crossbar coils 43 of the first andthird crossbars 34, 38.

For example, a single wire 32 may be run through the frame coil 30 (orhollow, tubular frame member) of the first frame 22 one or more times,at which point free wire ends at opposite ends of the first frame 22 arerun toward each other, through the crossbar coils 43 in oppositedirections. The ends of the wire 32 may then be extended through thecrossbar coils 43 toward opposite ends in each case, and looped backinto the other of the first and third crossbar coils 43, whereby theexcess free ends can be clipped and crimped, tied, or further stabilizedas necessary.

Alternative wiring configurations for linking the first frame 22 and thefirst and third crossbars 34, 38 may be employed. Moreover, wire endsmay be completely extended through the crossbar coils 43 and loopedaround the first frame 22 before their exchange into the crossbar coils43 a second time. It should be understood that the second frame 24, thesecond crossbar 36, and the fourth crossbar 40 may be connectedsimilarly to the first frame 22, the first crossbar 34, and the thirdcrossbar 38, as described above, with the use of the single wire 35, forexample. In addition, further details regarding assembling the closuredevice are provided below.

Now referring to FIGS. 4 and 5, the closure device 20 is illustrated ina flatter configuration, without being pulled apart by the cords 25shown in FIG. 2. Each of the first and second frames 22, 24 define aplane which is at least partially covered by the sheets 26, 28 ofbiocompatible material. Preferably the frames 22, 24 are substantiallycovered or completely covered by the sheets 26, 28 of biocompatiblematerial. The sheets 26, 28 of biocompatible material provide a coveringover the frames 22, 24, which is designed to cover or occlude a bodilypassageway.

When deployed (see FIGS. 2-3, e.g.), the first and second crossbars 34,36 are connected by the coupling member 44 at the first connection point50. As described above, each of the first and second crossbars 34, 36are configured to bend away from the first connection point 50. As such,the first crossbar 34 is configured to extend in an arc concave to thefirst frame 22 plane when deployed, and the second crossbar 36 isconfigured to extend in an arc convex to the first frame 22 plane whendeployed. Accordingly, the second crossbar 36 is configured to extend inan arc concave to the second frame 24 plane when deployed, and the firstcrossbar 34 is configured to extend in an arc convex to the second frame24 plane when deployed.

The third and fourth crossbars 38, 40 are configured similarly to thefirst and second crossbars 34, 36. Thus, the third and fourth crossbars38, 40 are connected by the coupling member 46 at the second connectionpoint 52, and each of the third and fourth crossbars 38, 40 areconfigured to bend away from the second connection point 52 whendeployed. As such, the third crossbar 38 is configured to extend in anarc concave to the first frame 22 plane when deployed, and the fourthcrossbar 40 is configured to extend in an arc convex to the first frame22 plane when deployed. Conversely, the fourth crossbar 40 is configuredto extend in an arc concave to the second frame 24 plane when deployed,and the third crossbar 38 is configured to extend in an arc convex tothe second frame 24 plane when deployed.

Referring to FIGS. 2 and 3, the closure device 20 may additionallyinclude a delivery bar 54 to enhance delivery or retrieval of theclosure device 20. The delivery bar 54 may have a flexible,substantially linear structure configured for releasable attachment to adelivery release member. In the event that the closure device 20 isfound to be not properly positioned, anchorage of the delivery bar 54 toa delivery release member permits the closure device 20 to be withdrawnand/or repositioned as necessary.

The delivery bar 54 may be comprised of a hollow tubular member, such asa coil or other hollow tube, or it may include merely a wire or othersuitable member. In FIGS. 2 and 3, the delivery bar 54 is shown having ahollow coil 56, similar to the crossbar coils 43 and the frame coils 30.The delivery bar 54 has a retention member 58, such as a wire, disposedwithin the coil 56 and linked to the second frame 24; however, it shouldbe understood that the delivery bar 54 could alternatively be linked tothe first frame 22 or one of the crossbars 34, 36, 38, 40. The deliverybar has terminal delivery bar ends 60 that are connectively linked tothe second frame 24 at discontinuous sites thereon; in other words, theterminal deliver bar ends 60 are connectively linked to separate siteson the second frame 24. The terminal delivery bar ends 60 may also bespaced apart from the terminal crossbar ends 42 of the second and fourthcrossbars 36, 40. The terminal ends 60 may form loops to surround thewire 35 and/or the coil 30 of the second frame 24. For example, theretention members 58 may include loops extending therefrom andsurrounding the second frame 24 to link the delivery bar 54 to thesecond frame 24.

In one aspect, the delivery bar 54 may include one or more graspingmembers (not shown) having a grasping structure or shape suitable (forexample, loop, knob, ball, hook, and the like) for releasable attachmentto a delivery release member facilitating delivery of the closure device20. However, in other embodiments, a delivery release member may attachto the coil 56 or retention member 58 of the delivery bar 54 fordeployment to close a bodily passageway. One or more delivery bars 54may be used, or none may be used. In some embodiments, the delivery bar54 may be connected to the sheet 28 of biocompatible or bioremodelablematerial using any suitable method of attachment.

The delivery bar 54 may be attached to the second frame 24 usingsutures, clips, wires, staples, adhesives, crimping, tying, combinationsthereof, or any other suitable attachment materials or attachmentstructures known to those of skill in the art.

The crossbars 34, 36, 38, 40 and the delivery bar 54 may be formed asflexible, substantially linear structures that may be configured from,or configured to include, a substantially one-dimensional tube, coil,bar, cannula, or wire having a circular, elliptical or polygonalcross-sectional shape. A crossbar 34, 36, 38, 40 or delivery bar 54 ispreferably hollow in nature. This can facilitate linkage to other devicecomponents using retention members 32, 35, 58, such as wires, forexample. It should be noted, however, that any materials providingflexibility and interconnectivity can be used for the crossbars 34, 36,38, 40, delivery bar 54, and frame coils 30, including shape memorymaterials, braided wires and the like.

In the closure devices 20 of the present invention, one or more wires32, 35, 58 may be used for interconnecting the frames 22, 24, crossbars34, 36, 38, 40, and/or delivery bar 54. In addition to wires 32, 35, 58and coupling members 44, 46, the above described structural componentsmay be connected to one another using any suitable attachment meansknown to those of skill in the art, including but not limited to thesutures, adhesives, soldering, welding, crimping, and the like.

A closure device 20 of the present invention may be made of flexiblematerials so that the closure device is sufficiently collapsible to beretained and delivered from a variety of catheter delivery sizes,including 6-15 French size, preferably 8-12 French size. Accordingly,one or more of the component device parts of the closure device 20 maybe made from flexible, radiopaque, materials such as platinum and/or orshape memory alloy materials, such as Nitinol, including those describedin U.S. Pat. Nos. 4,665,906, 5,108,420, the disclosures of which areincorporated by reference herein.

Shape-memory materials may be included in a number of component closuredevice 20 parts, including, but not limited to the frame coils 30, thecrossbar coils 43, the delivery bar coil 56, and the retention members32, 35, 58. The shape-memory materials, including Nitinol alloys, may beutilized whereby the alloy materials are compressed or partiallyexpanded in their martensitic state and fully expanded in theiraustenitic state. A specific shape memory alloy may be chosen so thatthe frames 22, 24 and the crossbars 34, 36, 38, 40 are in the austeniticstate at body temperature. Prior to insertion into the body, the closuredevice 20 may be maintained at a low temperature within the martensiticrange. Upon delivery to a desired bodily location, the closure device 20may be warmed to at least the A_(f) temperature so that it can expand toits desired configuration.

Suitable shape-memory materials and their use in medical applications isdisclosed in U.S. Pat. No. 3,012,882 to Muldawer et al.; U.S. Pat. No.3,174,851 to Buechler et al.; U.S. Pat. No. 4,665,906 to Jervis; U.S.Pat. No. 5,108,420 to Marks; U.S. Pat. No. 5,769,796 to Palermo et al.,U.S. Pat. No. 5,846,247 to Unsworth et al.; and U.S. Pat. No. 6,451,052to Burmeister et al., the disclosures of which are expresslyincorporated herein by reference.

Preferably, the frames 22, 24 are made from, or at least include,flexible radiopaque materials, and/or shape memory alloy materials. Theterm “radiopaque” refers to a non-toxic material capable of beingmonitored or detected during injection into a mammalian subject by, forexample, radiography or fluoroscopy. The radiopaque material may beeither water soluble or water insoluble. Examples of water solubleradiopaque materials include metrizamide, iopamidol, iothalamate sodium,iodomide sodium, and meglumine. Examples of water insoluble radiopaquematerials include tantalum, tantalum oxide, and barium sulfate, whichare commercially available in the proper form for in vivo use. Otherwater insoluble radiopaque materials include, but are not limited to,gold, tungsten, stainless steel, and platinum. The coils 43 of thecrossbars 34, 36, 38, 40 and the coil 56 of the delivery bar 54 may bemade of the same or similar materials.

In a preferred embodiment, the coils or tubular members 30 of the frames22, 24 are made of platinum or Nitinol. Preferably, the retentionmembers 32, 35, 58 used for linking components of the above-describedclosure device 20 include or are made from a suitable shape memory alloymaterials. In a preferred embodiment, the retention members 32, 35, 58are wires that are made from a Nitinol alloy.

Radiopaque marker materials may be used in the device componentsdirectly or they may be added to one or more components of the closuredevice 20 so as to render them radiopaque or MRI compatible. Inparticular, radiopaque materials, fillers, metallic marker bands orpowders may be included into one or more of the coils 30 of the frames22, 24, the retention members 32, 35, 58, the sheets 26, 28 ofbiocompatible material, the coils 43 of the crossbars 34, 36, 38, 40,the coil 56 of the delivery bar 54, and/or the delivery catheter tofacilitate radiographic visualization of the device during theimplantation process. Preferably, one or more of the frame coils 30,crossbar coils 43, and/or delivery bar coil 56 is made from or includesa radiopaque material (such as platinum) to facilitate radiographicvisualization.

Exemplary radiopaque marker materials include but are not limited to,platinum, gold, tungsten, tantalum, tantalum powder, bismuth, bismuthoxychloride, barium, barium sulphate, iodine and the like. Metallicbands of stainless steel, tantalum, platinum, gold, or other suitablematerials, can include a dimple pattern, which can further facilitateultrasound or X-ray identification.

Radiopaque markers may be introduced in any form suitable for therendering the closure device radiopaque or MRI compatible. In addition,the radiopaque materials can be incorporated in the closure device orassembly components by a variety of common methods, such as adhesivebonding, lamination between two material layers, vapor deposition, andthe materials and methods described in U.S. Pat. Appl. Publ. No.2003/0206860, the disclosure of which is incorporated herein byreference.

Sutures 29 for linking elements of the closure device 20 to one anothermay be made from a variety of suture types, including braided ormonofilament. Sutures 29 may be made from polyester, polypropylene,polyglycolic acid, polytetrafluoroethylene (PTFE), SIS, nylon, silk orany of a variety of absorbable or nonabsorbable suture materials knownin the art. The sutures 29 may be treated or coated with radiopaquematerials to facilitate visualization of the device by radiography orfluoroscopy. The sutures 29 may also be coated with antibiotics or otherantimicrobial agents. Exemplary suture materials include TEVDEK II®, abraided polyester suture material impregnated with PTFE; DEKLENE II®, apolypropylene monofilament suture material, and nylon monofilamentsuture material, all of which are manufactured by Genzyme Biosurgery ofCambridge, Mass. Preferred suture materials include non-absorbablepolypropylene sutures, such as PROLENE™ 6-0 mil (0.1524 mm) diameter(Ethicon Inc., Piscataway, N.J.).

As an alternative to sutures 29, tissue adhesives may be used to linkelements of the above disclosed closure device 20 to one another, forexample, to link the sheets 26, 28 of biocompatible sheet material tothe frames 22, 24. An exemplary tissue adhesive is BioGlue® (CryoLife,Inc.). Other suitable adhesives include fibrin-, fibrinogen-, andthrombin-based sealants, bioactive ceramic-based sealants, andcyanoacrylate sealants, including, but not limited to, Vitex (V.I.Technologies, NY; comprising thrombin:fibrinogen in a 1:1 ratio); Quixil(Omrix Biopharm SA, Brussels); Dermabond, an octylcyanoacrylate tissueadhesive (Bruns and Worthington (2000) Am. Fam. Physician 61:1383-1388);Tisseel (Baxter International, Deerfield, Ill.); Hemaseel APR(Haemacure, Sarasota, Fla.); PlasmaSeal (Plasmaseal, San Francisco,Calif.); AutoSeal (Harvest Technologies, Norwell, Mass.); Floseal(Fusion Medical Technologies, Mountain View, Calif.); Bioglass (U.S.Biomaterials, Alachua, Fla.); CoStasis (Cohesion Technologies); MedProMonth (1999) 9:261-262; and MedPro Month (2000) 10:86-91.

Now with reference to FIGS. 9 and 9A-9N, an embodiment of a method 100of making a closure device 20 in accordance with the principles of thepresent invention is illustrated. The method 100 includes a step 102 ofthreading one or more first retention members 32 through one or moretubular members 30 to create a first frame 22. The tubular members 30may be provided as coils, and the retention members 32 may be providedas wires, as described above. In this embodiment, two coils 30 (30′ and30″) are threaded onto a single wire 32. As shown in FIG. 9A, the wires32 are threaded through each coil 30 twice, such that portions of thewire 30 run through the lumen of each coil 30 twice. The wire 32 ispulled to circularize the coils 30 and form them into a ring shape, eachframe coil 30 defining a hemispheric coil ring portion.

Now with reference to FIG. 9B, in this embodiment, the wire 32 isthreaded through one of the coils 30 a third time, so that the ends ofthe wire 32 extend from the first frame 22 at opposite sides of theframe 22. The wire 32 is pulled to bring the ends 33 of each of thecoils 30′, 30″ close together with substantially no gap g, or a verysmall gap g between the ends 33. At this time, the diameter of the frame22 may be verified to determine whether the diameter is the appropriatesize for the desired application of the closure device 20.

With reference to FIGS. 9 and 9C-9E, the method 100 includes a step 104of threading the first retention member(s) 32 through a first crossbar34 and a third crossbar 38. The first crossbar 34 may be provided as acoil, as explained above. Although a single first retention member 32 isdescribed herein for connecting the frame coils 30 and the firstcrossbar 34, it should be understood that a plurality of retentionmembers 32 could be used. In some embodiments, the method 100 couldinclude a step of disposing a coupling member 44, such as a marker band,onto the first crossbar 34.

With reference to FIG. 9D, another end of the retention member, wire 32,formerly shown on the left side of the page in FIG. 9C is also threadedthrough the first crossbar 34. As such, the wire 32 is runs through thelumen of the first crossbar 34 twice, and extends from each terminal end42 of the first crossbar 34 at opposite sides of the first frame 22. Theterminal ends 42 are pulled close to the ends 33 of the frame coils 30′,30″.

Now with reference to FIG. 9E, a “third” crossbar 38 (the secondcrossbar 36 has not yet been added to the closure device 20, and it willbe described below) is threaded onto the wire 32. The wire 32 isthreaded through the lumen of the third crossbar 38 twice, from eachside of the frame 22. Therefore, the wire 32 end shown at the right sideof FIG. 9D now appears on the left side of FIG. 9E after being threadedthrough the lumen of the coil of the third crossbar 38, and the wire 32end shown at the left side of FIG. 9D now appears on the right side ofFIG. 9E after being threaded through the lumen of the coil of the thirdcrossbar 38. The wire 32 is pulled tight to bring the terminal ends 42of the third crossbar 38 near the terminal ends 42 of the first crossbar34 and the ends 33 of the first frame coils 30′, 30″ Prior to threadingthe third crossbar 38 onto the wire 32, a coupling member 46, such as amarker band, may be threaded onto the third crossbar 38.

Thereafter, the wire 32 may be fastened, or it may be threaded throughone or more of the frame coils 30′, 30″, or coils of the first and thirdcrossbars 34, 38 as space within the lumens permits. For example, thewire 32 as shown in FIG. 9E may be threaded back through the coil 30″,from the right side of FIG. 9E to the left side, so that each wire 32end is located on the left side of the figure. After such threading, thewire 32 will then be threaded through each of the frame coils 30′, 30″atotal of three times, which may be the maximum of amount of wire forwhich there is space in the lumens in some embodiments. For example, insome embodiments, the frame coils 30′, 30″ and crossbars 34, 38 maycomprise 0.023 inch diameter Platinum coil, and the wire 32 may comprise0.0065 inch diameter Nitinol wire, by way of example.

At this time, since the crossbars 34, 38 still only have the wire 32threaded through each of them twice thus far, one end of the wire 32could then be threaded through the first crossbar 34, while the otherend of the wire 32 could be threaded through the third crossbar 38.Accordingly, both ends of the wire would then be located on the rightside of FIG. 9E.

In some embodiments, one or both ends of the wire 32 may be wrappedaround the left edge of the frame 22 before it is threaded back throughthe crossbars 34, 38 for a third run through the crossbars 34, 38. Forexample, referring to FIG. 9F, the wire 32 can be seen wrapped around aside of the frame 22. In this embodiment, the wire 32 is wrapped aroundstrands of itself, however, the wire could be wrapped around one or bothof the coils 30′, 30″. The wire 32 ends may be cut or clipped, with wirecutters for example, as close as possible to the frame coils 30′, 30″

The method 100 includes a step 106 of fastening the first retentionmember(s) 32 to hold together the first tubular member(s) (coils 30′,30″), the first crossbar 34, and the third crossbar 38. Accordingly, theends of the wire 32, the frame coils 30′, 30″, and/or the coils of thecrossbars 34, 38 may be crimped with pliers to hold the wires 32 inplace; however, it should be understood that the wires 32 could befastened in any other suitable manner, such as by welding, soldering,tying, press-fitting them back into one of the coils 30′, 30″ orcrossbars 34, 38, or using adhesives, by way of example. The coils 30′,30″ may be pulled to remove most of any gap or exposed wire 32, as shownin FIG. 9F.

The method 100 further includes a step 108 of threading one or moresecond retention members 35 through one or more second tubular members30′″, 30″″ to create a second frame 24. With reference to FIG. 9G, inthis embodiment, a single wire is used as the second retention member35. The wire 35 is threaded through two coils 30′″, 30″″, eachcomprising a portion of the second frame 24. The wire 35 is threadedthrough one of the second frame members 30″″ twice and the other secondframe member 30″″ three times, similarly to the threading of the firstframe 22 described in FIG. 9C. The wire 35 is pulled tight to bring theends 33 of the coils 30′″, 30″″ together and form the frame coils 30′″,30″″ into a ring shape, each frame coil 30′″, 30″″ defining ahemispheric coil ring portion.

In addition, the method 100 includes a step 110 of threading the secondretention member(s) 35 through a second crossbar 36 and a fourthcrossbar 40. In FIG. 9G, the wire 35 is shown threaded through the lumenof the second crossbar 36, which may be a coil, as described above. Thesecond crossbar 36 is not provided with its own coupling member becauseit will share a coupling member located on the first crossbar 34. Theaddition of the fourth crossbar 40 will be described below.

With reference to FIGS. 9 and 9H, the method 100 includes a step 114 ofattaching a central portion of the first crossbar 34 to the secondcrossbar 36. In this embodiment, the second crossbar 36 is threadedthrough the coupling member 44 that is located around the first crossbar34. It should be understood that the first and second crossbars 34, 36could additionally or alternatively be attached to each other by othersuitable means, some of which are described above.

Thereafter, the end of the wire 35 located at the left side of FIG. 9Hmay be threaded through the second crossbar 36 such that the wire 35passes through the lumen of the second crossbar 35 twice, similarly tothe way the first crossbar 38 was threaded as shown in FIG. 9D. Forexample, referring now to FIG. 9I, the wire 35 is shown threaded throughthe second crossbar 36 twice. In addition, FIG. 9I shows the wire 35being threaded through the fourth crossbar 40. In FIG. 9I, the closuredevice 20 has been flipped 180° from the orientation in which it wasshown in Fig. H. Like the second crossbar 36, the fourth crossbar 40does not have its own coupling member because it will share a couplingmember with the third crossbar 38.

Referring now to FIGS. 9 and 9J, the method 100 includes a step 116 ofattaching the third crossbar 38 to the fourth crossbar 40. In thisembodiment, the fourth crossbar 40 is threaded through the couplingmember 46 located around the third crossbar 38 to attach the thirdcrossbar 38 to the fourth crossbar 40. The wire 35 end that is notalready threaded through the fourth crossbar 40 may then be threadedthrough the lumen of the fourth crossbar 40. Both free ends of the wire35 may then be pulled to substantially cover the exposed portions of thewire 35 with coils. The terminal ends 42 of the second and fourthcrossbars 36, 40 may be pulled near the ends 33 of the coils 30′″, 30″″,similarly to the configuration of the first frame 22, the first crossbar34, and the third crossbar 38, as shown in FIG. 9E.

The wire 35 may be optionally threaded through one or more of the coils30′″, 30″″ and/or the second and fourth crossbars 36, 40 again, asdesired. For example, one end of the wire 35 may be threaded through thecoil 30″″, such that the wire 35 is then threaded through each of thesecond frame coils 30′″, 30″″ three times. The ends of the wire 35 willthen be located on the same side of the second frame 24. One end of thewire 35 may then be threaded once more through each of the second andfourth crossbars 36, 40, resulting in the wire 35 being threaded througheach of the second and fourth crossbars 36, 40 a total of three times.Prior to being threaded through the crossbars 36, 40 a third time, oneor both ends of the wire 35 could be wrapped around the coils 30′″, 30″″or wire 35 of the second frame 24, if desired.

Referring now to FIGS. 9 and 9K, the method 100 further includes a step112 of fastening the second retention member(s) 35 to hold together thesecond tubular member(s) 30′″, 30″″, the second crossbar 36, and thefourth crossbar 40. The wires 35 are pulled tight, cut, and fastened,for example, by crimping or other suitable means, such as thosedescribed above with respect to fastening the wire 32 of the first frame22. In some embodiments, one or more of the coils 30′″, 30″″ of theframes 22, 24 or the coils of the crossbars 36, 40 may be crimped tohold the wire 35 in place. The frame coils 30′″, 30″″ may be stretchedto substantially cover the exposed portions of the wire 35.

The coupling members 44, 46 may be slid onto a central portion of thecrossbars 34, 36, 38, 40, for example, a portion not more than 30% fromthe geometric center of the crossbars 34, 36, 38, 40, by way of example.The coupling members 44, 46 may be partially flattened to tighten themaround the crossbars 34, 36, 38, 40, for example, by crimping, butpreferably the coupling members are not crimped so tight as to kink thecoils of the crossbars 34, 36, 38, 40. In addition, or in thealternative, sutures may be secured around the coupling members 44, 46to hold them in place. It should be understood that the first and secondcrossbars 34, 36 and the third and fourth crossbars 38, 40 may beattached to each other in any other suitable manner, and they need notuse coupling members 44, 46; and the coupling members 44, 46 need not bemarker bands.

The method 100 further includes a step 118 of threading one or morethird retention members, such as a wire 58, through a delivery bar 54.In this embodiment, the delivery bar 54 includes a hollow coil throughwhich the wire 58 is threaded.

Referring now to FIG. 9L, a method of threading the wire 58 through thecoil of the delivery bar 54 is illustrated. Briefly, the delivery barwire 58 is passed through the coil of the delivery bar 54 three times.The loop structures 62 a, 62 b can be formed by extending the wire 58through the coil of the delivery bar 54, looping the wire 58 backtowards each open end 64, 66 of the coil of the delivery bar 54, pullingthe wire 58 at each delivery bar 54 coil end 64, 66 back through thecoil of the delivery bar 54 in the opposite direction to achieve adesired loop size, and cutting off the excess free anchor wire ends 68a, 68 b extending from each end 64, 66 of the coil of the delivery bar54. The free wire ends 68 a, 68 b may be looped back, knotted or crimpednear the ends 64, 66 of the coil of the delivery bar 54 to stabilize theterminally disposed loop structures 62 a, 62 b or free wire ends 68 a,68 b proximal to each end 64, 66 of the coil of the delivery bar 54. Byconfiguring the loop structures 62 a, 62 b to be wider than the diameterof the coil of the delivery bar 54 at each coil end 64, 66, the graspingmembers or loop structures 62 a, 62 b are frictionally engaged by orsecured by the coil of the delivery bar 54.

Now referring to FIG. 9M, the loop structures 62 a, 62 b, shown in FIG.9L, are looped around the frame coils 30′″, 30″″ of the second frame 24.In other words, FIG. 9L shows an exemplary method of created the loopstructures 62 a, 62 b, but in this embodiment, the loop structures 62 a,62 b are created around the frame coils 30′″, 30″″, rather than merelyaround nothing as shown in FIG. 9L.

Referring to FIGS. 9 and 9N, the method 100 further includes a step 120of fastening the third retention member(s) 58 to one or more of thefollowing: the first tubular member(s) 30′, 30″, the second tubularmember(s) 30′″, 30″″, the first retention member(s) 32, and/or thesecond retention member(s) 35. In the embodiment of FIG. 9N, the thirdretention member, wire 58, is fastened around the coils 30′″, 30″″ ofthe second frame 24, at a location spaced apart from the terminal ends42 of the second and fourth crossbars 36, 40. The loops 62 a, 62 b ofthe wire 58 are secured around a central portion, not more than 30% fromthe geometric center, of the frame coils 30′″, 30″″, however, it shouldbe understood that in other embodiments, the delivery bar 54 need not besecured around central portions of the frame coils 30′″, 30″″, The endsof the wires 58 are pulled tight to remove the slack and the loops 62 a,62 b are wrapped snugly around the frame coils 30′″, 30″″ It should beunderstood that the delivery bar 54 may alternatively be fastened to thesecond frame 24 or the first frame 22 in any other suitable manner, suchas described above.

The ends of the wire 58 are cut at a location very close to the coil ofthe delivery bar 54. The coil of the delivery bar 54 and/or the wire 58may be crimped to fasten the delivery bar 54 in place. The coil of thedelivery bar 54 may also be stretched to substantially eliminate exposedportions of the wire 58.

The crossbars 34, 36, 38, 40, and/or the first and second frames 22, 24may be heat treated. Heat treating the crossbars 34, 36, 38, 40 mayassist with configuring the crossbars 34, 36, 38, 40 to bend toward aflat position, such as shown in FIGS. 4 and 5. Heat treating the frames22, 24 may assist with biasing the frames toward an expanded state.

In a further aspect, referring now to FIGS. 10A-10C, a closure deviceassembly 70 for delivering a closure device 20 according to the presentinvention is provided. The closure device assembly 70 includes adelivery catheter housing 72, a delivery release member 74, and apre-loaded, collapsibly disposed closure device 20. The delivery releasemember 74 includes one or more structural portions for releasableattachment to at least one portion of the closure device 20, such as adelivery bar 54. In a further aspect, the delivery release member 74 ispreferably positioned in a locking catheter preventing inadvertentrelease of the closure device 20 when held in a compressed state insidethe delivery catheter housing 72.

The delivery release member 74 may include a structure configured forreleasable attachment to the delivery 54 or other portion of the closuredevice 20. The delivery release member 74 may be configured as anengaging member or a release member having an engaging structurecomplementary to the portion of the closure device 20 to which it isdesigned to engage, for releasable attachment thereto. For example, thedelivery release member 74 may include a crossbar engaging portion, aframe engaging portion, or a delivery bar engaging portion 76. Theengaging portion may include a ball, hook, loop, pair of cups or jaws,or any other suitable member capable of releasable attachment to thedelivery bar 54 or other portion of the closure device 20. In oneembodiment, the delivery release member 74 includes biopsy forceps. Inanother embodiment, the delivery release member 74 includes one or morehook-release structures.

Upon disengagement of the delivery bar 54 from the delivery releasemember 74, for example, the covered first frame 22 can be released so asto cover an opening of the bodily passageway, whereby the second frame24 is secured to the opposite end of the bodily passageway, therebysandwiching the closure device 20 around and through a bodilypassageway, such as a PFO having an opening 9 between a septum primum 7and a septum secundum 8.

In one embodiment, the delivery release member 74 includes an engagingstructure 76 in the form of biopsy jaws or cups to facilitate releasablelinkage to the delivery bar 54 of the closure device 20. As describedabove, the delivery bar 54 may be formed from a delivery bar coil 56having a wire 58 extending longitudinally therethrough. The engagingstructure 76 may be configured to releasably link to the coil 56 of thedelivery bar 54, by way of example.

As described above, the closure device 20 is made from sufficientlyflexible materials to enable the device 20 to be collapsibly disposed ina relatively small delivery catheter housing 72 (including 8 to 12French). The closure device 20 may be preloaded at the tip of thedelivery catheter housing 72 in an unexpanded, first configuration. Whenthe closure device 20 is expelled from the delivery catheter housing 72,it may expand to a second, expanded configuration, particularly when theclosure device 20 is made from shape memory materials. Non-shape memorymaterials, such as stainless steel and the like, may be used for closuredevices 20 requiring a lower degree of compression or expansion uponrelease.

In a preferred embodiment, the closure device assembly 70 includes adelivery catheter housing 72 with a curved flexor catheter sheath, and acollapsibly disposed closure device 20 preloaded at the sheath tip andconnected to a delivery release member 74, such biopsy forceps 76 or ahook held within a locking catheter 78. In a particularly preferredembodiment, the closure device assembly 70 includes a curved 8-12 Frenchdelivery catheter; a 4 or 5 French locking catheter 78 holding thebiopsy forceps 76, and a collapsibly disposed closure device 20. Flexor®Introducer Sets (Cook Medical Inc., Bloomington, Ind.) provide apreferred source of delivery catheters for use in the present invention.

The delivery catheter housing 72 may be configured for “long wire” or“over-the-wire” (OTW) delivery or for “short wire” or rapid exchange(RE) delivery procedures known to those of skill in the art.Accordingly, the delivery catheter housing 72 may be structurallymodified with apertures or modified lumenal portions to allow exchangefrom the angioplasty wire guide to the delivery catheter housing 72 byRE without the need to replace the wire guide with an exchange-lengthguide wire before exchanging the catheters. Exemplary RE catheters thatmay be used to deliver the closure device 20 of the present inventionare described in U.S. Pat. Nos. 5,690,642; 5,814,061; 6,371,961; andU.S. Pat. Application Nos. 2005/0070794; 2005/0125050; and 2005/0070821,the disclosures of which are expressly incorporated by reference herein.

To enhance the shelf life of the closure device containingbioremodelable materials, the closure device 20 may be lyophilized in anelongated form inside a cartridge sheath having a similar inner diametersheath size as the delivery catheter housing 72 (for example, 8-12French size). In view of their low device profile, closure devices 20 ofthe present invention can be delivered and securely deployed from asingle, tip preloaded delivery catheter for immediate and completepassageway closure in as little as 15 minutes.

With reference to FIG. 11, an alternative closure device assembly 170 isillustrated including a preloaded, collapsibly disposed closure device20, such as the one depicted in FIGS. 2-6. The closure device assembly170 includes a collapsibly disposed closure device 20 disposed near thedistal tip of a delivery catheter 172. The closure device assembly 170includes a delivery catheter housing 172 and a delivery bar releasemember 174 in the form of a smaller, coaxially positioned lockingcatheter 178 connected to a hook 176 that is subject to a spring tensionrelease mechanism. The linkage between the hook 176 and the delivery bar54 can facilitate accurate placement and uncoupling of the closuredevice 20 from the delivery catheter 72 in connection with closuredevice 20 deployment.

The distal end of the locking catheter 178 includes a hollow cannulaoverhanging at least a portion of the hook 176, whereby the springtension release mechanism prevents premature disengagement of thedelivery bar 54 from the hook 176 in the tip-preloaded closure device 20or following retraction of the delivery catheter 172 or followingextension of the locking catheter 178 out of the delivery catheter 172during delivery of the device.

In one embodiment, the Gunther Tulip™ Vena Cava filter delivery system(Cook Inc., Bloomington, Ind.) provides an exemplary locking catheter178 (a metal cannula in this case) for releasable attachment anddelivery of closure devices 20, including those configured to include adelivery bar 54 as described above. Components in the Gunther Tulip VenaCava filter delivery system, including the hook, delivery sheath, orlocking catheter, can be shape-modified or size-modified to accommodatea variety of closure device sizes or grasping members, includingdelivery bars 54 or other portions of the closure device 20.

In a further aspect, referring to FIGS. 10A-10C and FIG. 12, the presentinvention provides a method for closing or occluding a bodily opening ina patient using any variation of the above described closure device 20or closure device assemblies 70, 170. In a preferred embodiment, amethod 200 for closing or occluding a septal opening, such as a PFOusing a closure device assembly is provided herein.

By way of example, FIGS. 10A-10C depict an exemplary method for closinga PFO with an exemplary closure device assembly 70. An exemplary method200 for delivering any variation of the above-described closure device20 includes a step 202 of providing a closure device assembly 70,including a delivery catheter housing 72, a delivery release member 74,and a closure device 20 in accordance with the principles of a presentinvention described herein. The method 200 may further include passing astiff guide wire through a suitable multi-purpose catheter andpositioning the guide wire in the left atrium 4 across a bodilypassageway, such as a PFO.

The delivery catheter housing 72 of the closure device assembly 70 isthen introduced over the wire (not shown) into the patient. The method200 includes a step 204 of advancing the delivery catheter housing 72through a bodily passageway. Accordingly, the delivery catheter housing72 is advanced through a bodily passageway, depicted here as a PFOhaving an opening 9 between a septum primum 7 and a septum secundum 8,and the delivery catheter 72 is positioned into the left atrium 4 of apatient. Before releasing the closure device 20 or any part thereof, itsposition may be assessed by contrast media injection though the deliverycatheter housing 72, by way of example.

The method 200 further includes a step 206 of releasing a first frame 22of the closure device 20 from the delivery catheter housing 72 proximateto the first opening 9′ of the bodily passageway 9. Followingconfirmation of left atrium 4 positioning, in this embodiment, thecovered first frame 22 is released from the delivery catheter housing 72into the left atrium 4 proximate to the distal first opening 9′ of thePFO. This may be performed by beginning to retract the delivery catheterhousing 72 into the opening 9.

The method 200 includes a step 208 of retracting the delivery catheterhousing 72 through the bodily passageway 9 and positioning the deliverycatheter housing 72 proximate to a second opening 9″ of the bodilypassageway 9. Therefore, following release of the covered first frame 22from the distal end of the delivery catheter housing 72, the deliverycatheter housing 72 is retracted through the PFO passageway 9. Thecrossbars 34, 36, 38, 40 may be partially or fully released into theopening 9 during the retraction of the delivery catheter housing 72through the opening 9. After being retracted through the opening 9, thedelivery catheter housing 72 is positioned in the right atrium 2 nearthe proximal second opening 9″ of the PFO.

The method 200 further includes a step 210 of disengaging the closuredevice 20 from the delivery release member 74 and releasing the secondframe 24 to release the closure device 20 proximate to the secondopening 9″ of the bodily passageway 9, wherein the closure device 20 issecured to tissue portions 7, 8 surrounding the bodily passageway 9,thereby closing the bodily passageway 9. Accordingly, following properconfirmation of right atrium 2 closure device 20 positioning, thelocking catheter sheath 78 may be pulled back to disengage the engagingstructure 76 of the delivery release member 74 from the delivery bar 54connected to the second frame 24, thereby releasing the anchor deliverybar 54 and second frame 24 into the right atrium 2 near the proximalsecond opening 9″ of the PFO 9. Alternatively, when a locking catheteris not used, the delivery catheter housing 72 may be retracted torelease the delivery bar 54 and/or the second frame 24 from the end ofthe delivery catheter housing 72.

The closure device 20 is preferably self-expanding and retains itsoriginal expanded shape following release. For example, upon releasefrom the delivery catheter housing 72, the first and second frames 22,24 expand, springing back against the septum primum 7 and septumsecundum 8 on each side of the PFO 9, thus anchoring the first frame 22,24 to each side 9′, 9″ of the PFO 9. The biocompatible sheets 26, 28covering the first and second frames 22, 24 cover and occlude the PFO 9.The delivery catheter housing 72, locking catheter 78, and biopsyforceps or other engaging device 76 are then removed.

Of course, in the alternative to the method 200, any method for closinga bodily passageway, including PFOs, may be practiced using any of theabove-described closure devices 20 or assemblies.

As an alternative to the pre-assembled over-the-wire assembly describedabove, one can alternatively introduce and position a wire guide througha suitable catheter or sheath near the site of the passageway opening;load the collapsible closure device 20 into the sheath; push the closuredevice 20 to the desired site with a biopsy forceps, pushing catheter,or other suitable pushing device, for example; and release the closuredevice 20 as described above.

Visualization of the closure device assembly 70, 170 within the interiorof the heart during deployment may be provided by various means. Forexample, fluoro-visible (or radio-opaque) dyes may be injected into thecardiac chambers and venous anatomy so that the chambers of the heartand the related vasculature are visible using a fluoroscopic device.This procedure, sometimes referred to as a venogram, allows the surgeonto locate a precise site and achieve proper device placement whenperforming an implant procedure.

Additionally, an ultrasonic probe may be positioned in the patient'sesophagus, on the surface of the patient's chest, or in the chest cavityadjacent or in contact with the exterior of the heart to ultrasonicallyimage the interior of the heart. In particular an intravascularultrasound (IVUS) catheter may be utilized in conjunction with one ofthe above closure device assemblies 70, 170 to provide ultrasonicimaging. Alternatively, an endoscope with a translucent bulb or balloonover its distal end may be introduced into the heart through the closuredevice assembly or through a separate incision in the wall of the heartto allow video-based or direct visualization of the interior of theheart. An angioscope introduced into the heart endovascularly through aperipheral vessel may also be used for intracardiac visualization.Fluoroscopy or magnetic resonance imaging (MRI) may provide anadditional means for visualization.

Sheaths, dilators, catheters, multi-purpose catheters, pushingcatheters, wire guides and needles used in the present invention can allbe conventional marketed products or modifications thereof. For example,sheaths can be formed from PTFE (such as Teflon) or polyamide (such asNylon) material, or a combination of materials such as an assemblyincluding an inner layer of PTFE, a flat wire coil over the PTFE forkink resistance, and a polyamide (Nylon) outer layer to provideintegrity to the overall structure and a smooth surface (as in theFlexor® Introducer Sets, Cook Medical Inc., Bloomington, Ind.). Dilatorscan be made from conventional dilator/catheter type materials such aspolyethylene, polyamide, polyurethane or vinyl, or any combination ofthese materials. Fittings provided for sheath/dilator assemblies can beconventional elements such as luer locks; the dilator and the lockingcatheter can have fittings allowing them to be locked to the sheathduring insertion and manipulation. Catheters can be made fromconventional materials such as polyethylene, polyamide, PTFE,polyurethane, and other materials. Assembly components, including biopsyforceps or hooks, may be separately contained in interlumenal sheathswithin the delivery catheter or they may be disposed through secondarylumenal portions formed in the delivery catheter, as in double lumencatheters and the like.

The delivery catheter housing 72, 172 includes a sheath having a lumendiameter sized to allow for the introduction of the closure device 20 toocclude the bodily passageway of interest. Illustratively, the innerdiameter (I.D.) of the delivery sheath may range from 6 to at least 15French or more, depending on the size of the closure device and thebodily passageway for closure. In preferred embodiments the deliverycatheter housing 72, 172 includes an inner diameter of 6 French(corresponding to an I.D. of about 0.087 inch), 7 French (correspondingto an I.D. of about 0.100 inch), 8 French (corresponding to an I.D. ofabout 0.113 inch), 12 French (corresponding to an I.D. of about 0.162inch), and 15 French (corresponding to an I.D. of about 0.197 inch).

A closure device 20 or assembly 70, 170 according to the presentinvention is particularly suited for closing septal heart defects,including PFOs and other atrial septal or ventricular septal defects.However, the closure device 20 can be similarly applied to closing oroccluding a variety of other heart openings, tissue openings, vessels,vessel punctures, ducts, and other tissue openings where closure isdesired.

In some instances it may be necessary to reposition or remove theclosure device 20, particularly when it includes sufficiently flexiblematerials or a sufficiently flexible structural configuration. This mayoccur where the device is not appropriately positioned or sized for aparticular bodily passageway and/or fails to completely seal thepassageway. In cases where it is necessary or advisable to repositionthe closure device 20 following initiation of deployment or prior tofull deployment, a delivery release member 74, 174 may be used toreposition the device. In this case, a delivery release member 74, 174remaining connectively linked to a delivery bar 54 or a frame 22, 24 orcrossbar 34, 36, 38, 40 may be pushed back into the side of the bodilypassageway holding the closure device 20 and pulled back into thedelivery sheath, at which point repositioning of the closure device 20can be initiated prior to full deployment (and release).

In cases where it is necessary or advisable to remove the closure device20 following full deployment, a suitable foreign body retrieval device,such as a snare, may be used to remove the device. The snare may bedelivered through the introducer sheath using a snare catheter.Preferred snares are commercially available under the trade namesNeedle's Eye® Snare (Cook Medical, Bloomington, Ind.) and MicrovenaAmplatz Goose Neck® Snare (ev3 Inc., Plymouth, Minn.). After positioningthe snare around the delivery bar 54 and advancing the delivery bar 54through the passageway 9 where the covered first frame 22 is held, theclosure device 20 can be pulled back into a delivery catheter sheath andremoved.

In some applications, it is advisable to measure the size of the bodilyopening prior to installation of the closure device 20. Measurement maybe made using a balloon catheter, for example. Further, in someapplications, it may be advisable to enlarge the bodily passagewaybefore closing it with a closure device 20. An angioplasty balloonand/or an occlusion balloon may be inflated within the interatrialseptum to enlarge the opening, by way of example, and to measure thesize of the opening.

It is intended that the foregoing detailed description be regarded asillustrative rather than limiting, and that it be understood that it isthe following claims, including all equivalents, that are intended todefine the spirit and scope of this invention.

Although the embodiments of this device have been disclosed as beingconstructed from wire having a round cross section, it could also be cutfrom a tube of suitable material by laser cutting, electrical dischargemachining or any other suitable process.

While the present invention has been described in terms of preferredembodiments, it will be understood, of course, that the invention is notlimited thereto since modifications may be made to those skilled in theart, particularly in light of the foregoing teachings.

What is claimed is:
 1. A method for closing a bodily passageway in apatient, the method comprising: providing a closure device assembly, theclosure device assembly comprising: a delivery catheter housing; adelivery release member; and a collapsibly disposed closure device, theclosure device comprising: a first frame; a sheet of biocompatiblematerial attached to the first frame; a first crossbar extending acrossthe first frame, the first crossbar having terminal crossbar endsconnectively linked to separate sites on the first frame; a secondcrossbar attached to the first crossbar at a connection point; and asecond frame, the second crossbar extending across the second frame, thesecond crossbar having terminal crossbar ends connectively linked toseparate sites on the second frame, wherein the first crossbar and thesecond crossbar are each configured to bend away from the connectionpoint when the closure device is deployed to close a bodily passageway;advancing the delivery catheter housing through the bodily passageway;releasing the first frame from the delivery catheter housing proximateto a first opening of the bodily passageway; retracting the deliverycatheter housing through the bodily passageway and positioning thedelivery catheter housing proximate to a second opening of the bodilypassageway; and disengaging the closure device from the delivery releasemember and releasing the second frame proximate to the second opening ofthe bodily passageway, wherein the closure device is secured to tissueportions surrounding the bodily passageway, thereby closing the bodilypassageway.
 2. A method for making a closure device for closing a bodilypassageway, the method comprising: threading at least one firstretention member through at least one first tubular member to create afirst frame; threading the at least one first retention member through afirst crossbar and a third crossbar; fastening the at least one firstretention member to hold together the at least one first tubular member,the first crossbar and the third crossbar; threading at least one secondretention member though at least one second tubular member to create asecond frame; threading the at least one second retention member througha second crossbar and a fourth crossbar; fastening the at least onesecond retention member to hold together the at least one second tubularmember, the second crossbar and the fourth crossbar; attaching a centralportion of the first crossbar to the second crossbar; attaching acentral portion of the third crossbar to the fourth crossbar; threadingat least one third retention member through a delivery bar; andfastening the at least one third retention member to at least one of thefollowing: the at least one first tubular member, the at least onesecond tubular member, the at least one first retention member, and theat least one second retention member.
 3. The method of claim 2, whereinthe retention members are provided as wires.
 4. The method of claim 3,wherein the tubular members, the crossbars, and the delivery bar areprovided as coils.
 5. The method of claim 4, wherein the step ofattaching a central portion of the first crossbar to the second crossbarcomprises threading the first crossbar and the second crossbar through afirst marker band; and wherein the step of attaching a central portionof the third crossbar to the fourth crossbar comprises threading thethird crossbar and the fourth crossbar through a second marker band. 6.The method of claim 4, wherein the at least one first tubular membercomprises two tubular members, and the first retention member is asingle retention member that is threaded through each of the two firsttubular members multiple times; and wherein the at least one secondtubular member comprises two tubular members, and the second retentionmember is a single retention member that is threaded through each of thetwo second tubular members multiple times.
 7. The method of claim 6,further comprising heat treating the tubular members and crossbars.